It has been disclosed that eburnamenine and dihydroeburnamenine derivatives of natural, semi-synthetic or synthetic origin possess anti-vascular spasmodic activity due to the peripheral resistance reducing effect thereof, and thus said compounds may be used for the treatment of vascular headaches originating from a functional vascular spasm or flow disturbances and hypertensive or arterioscterotic blood vessel crisis states. In spite of a higher dosage in case of oral administration the effect is slower than in the case of parenteral administration. If rapid activity is desirable, parenteral treatment is necessary in order to ensure a quick resorption.
Injectable solutions containing eburnamenine and dihydroeburnamenine derivatives are only partially known. The application thereof is particularly important from a therapeutic point of view, as these compounds also have brain vasodilator activity as opposed to the commercially available injectable solutions, possessing only hypotensive activity.
According to test results solutions of eburnamenine and dihydroeburnamenine derivatives with the conventionally used parenteral solvents are unstable and show a considerably lower activity in animal tests.
In FR-PS No. 2 191 891 a process is disclosed for the preparation of vincanol-containing solutions and lyophilized injectable compositions. The pH-value of the thus prepared aqueous solutions ranges from 6 to 7 and the solutions are rather unstable. According to our investigations the molecule is considerably isomerized at this pH-value. The preparation of the lyophilized molecule is at the same time less economical and according to the disclosure a solution containing not more than 2.5 mg. of vincanol per ml. may be prepared.
In the conventional aqueous solutions containing vincaminic acid methyl ester epimerization and in the aqueous solutions containing apovincaminic acid ethyl ester ester hydrolysis occur; thus the effectivity of such solutions becomes lower. A parenteral solvent is required, which is suitable for the preparation of stable injectable solutions from eburnamenine and dihydroeburnamenine derivatives of the formula I ##STR1## wherein X .about. y is ##STR2## wherein Z is hydroxy or cyano and R is hydrogen, an alkoxycarbonyl group having 2 to 6 carbon atoms which can be substituted by one or more halogen atoms or hydroxy groups or an aralkoxycarbonyl group.